miR-23b联合TGFβⅡ型受体拮抗剂治疗皮肤瘢痕的机制研究

First we reported and patented a truncated TGFβ type Ⅱ receptor antagonist (tTGFβRⅡ) to treat skin wound healing, and the newly discovered miRNA been linked to skin damage and scarring, meanwhile the miRNA related signal pathway play a key role in scar. but what miRNA is exactly related to scar. Pathological scar mainly include inflammation and hyperplasia, literature reported that TGFbeta, NF-kB and p38MAPK signal pathway were involved in pathological scar, however these signal pathway existed interaction and how these signal pathway interact is still unknown. our previous study showed that tTGF only inhibit TGFβsignal and showed single function. Thus, we hypothesis that tTGFβRⅡ combine miR-23b to inhibit TGFbeta, NF-κB and p38MAPK signal to stop scar production. This project would employ in vitro fibrosis cell and animal scar experiment by molecular and cell biology method, which will provide new insights in order to find new therapeutic strategies.

我们首先报道并专利了截断型TGFβⅡ型受体拮抗剂（tTGFβRⅡ）治疗皮肤瘢痕，而新近发现的miRNA被证实与皮肤损伤及瘢痕关系密切，其相关通路也与瘢痕有内在关联。但目前不清楚哪些miRNA与瘢痕是否关联。病理性瘢痕主要由炎症期和增生期组成。文献报道TGF-β、NF-κB、及p38MAPK等信号通路与瘢痕关系密切，并且这些信号通路存在交互联系。但是这些通路之间的关系又没有厘清。我们前期实验发现tTGFβ可阻断TGFβ信号通路，而miR-23b可以抑制NF-κB、p38MAPK信号通路。但tTGFβ只是阻断了TGFβ信号通路，表现为其作用单一性。因此，我们假设：tTGFβ联合miR-23b共阻滞TGF-β、NF-κB、及p38MAPK信号通路，多系统的抑制瘢痕生成，达到真正的标本兼治。本项目将采用体外细胞培养和动物实验相结合的病理类型，运用分子生物学、细胞生物学等技术为治疗瘢痕提供新的见解。

我们首先报道并专利了截断型TGFβⅡ型受体拮抗剂（tTGFβRⅡ）治疗皮肤瘢痕，而新近发现的miRNA被证实与皮肤损伤及瘢痕关系密切，其相关通路也与瘢痕有内在关联。但目前不清楚哪些miRNA与瘢痕是否关联。病理性瘢痕主要由炎症期和增生期组成。文献报道TGF-β、NF-κB、及p38MAPK等信号通路与瘢痕关系密切，并且这些信号通路存在交互联系。但是这些通路之间的关系又没有厘清。我们前期实验发现tTGFβ可阻断TGFβ信号通路，而miR-23b可以抑制NF-κB、p38MAPK信号通路。但tTGFβ只是阻断了TGFβ信号通路，表现为其作用单一性。因此，我们假设：tTGFβ联合miR-23b共阻滞TGF-β、NF-κB、及p38MAPK信号通路，多系统的抑制瘢痕生成，达到真正的标本兼治。本研究最主要的研究目标就是miR-23b、tTGFβRⅡ多肽拮抗剂对于抑制瘢痕生成的作用，实验结果表明联合用药优于单个用药。其次，构建小鼠皮肤创伤模型，研究瘢痕已存在或发生过程中细胞状态、下游信号通路之间的交互关系影响，阐明miR-23b、tTGFβRⅡ多肽拮抗剂抑制瘢痕增生的可能机制，为瘢痕的有效防治提供新的思路。